tbuckley/cabot-search huggingface dataset:
Abstract 37: Understanding the social determinants of guideline-based mammography adherence across race/ethnicity: Results from the 2016 California Health Interview Survey
Authors: Roman Johnson, Mieke Beth Thomeer
Journal: Cancer Research (2022)

Abstract Purpose: There is not a consensus concerning recommendations about breast cancer screening which has generated confusion about when and how often to undergo mammography screening in the population, yet there is limited population-based data about the extent to which patients adhere to various mammographic screening guidelines in practice. Our purpose was to evaluate population-based adherence to mammographic screening using criteria from major guideline-producing organizations across race/ethnicity to understand what social determinants of mammography adherence are associated with each guideline producing institution. Methods: Women aged 45-79 in the 2016 California Health Interview Survey were included. Self-reported mammographic screening within 1 or 2 years, according to major guideline-producing organizations (American Cancer Society [ACS], US Preventative Services Task Force [USPSTF], American College of Radiology [ACR], American College of Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression, adjusting for demographics, health care, insurance status, and BMI. Results: 7,551 women were included in this study. By age category, cross-sectional adherence to ACR/ACOG (annual screening) (65 to 67%) and USPSTF guidelines (biennial screening) ranged from 82-83% and with increasing age being generally associated higher adherence. The highest proportions of women undergoing mammographic screening were seen in women ages 60-69 (67% within last year, 85% within last 2 years). Statistically significant predictors of adherence to mammography screening included Latina race (OR 1.62, 0.18 SE), full time employment (OR 0.73, 0.09 SE), and not having a usual healthcare provider (OR 0.50, 0.12 SE), adjusted for demographics, health care, insurance status, and BMI. Conclusion: Frequency of screening increases with age with highest screening proportions in women ages 65-69 (66% within last year, 81% within last 2 years). For ACR/ACOG screening guidelines, adherence to mammography screening remains poorer in women with no usual source of care, given that their odds of exhibiting adherence was half that of women who did have a regular source of care and nearly 65 percent lower odds of those women with USPSTF mammography adherence. Key Words: Breast cancer, screening, race/ethnicity, guideline-based care Citation Format: Roman Johnson, Mieke Beth Thomeer. Understanding the social determinants of guideline-based mammography adherence across race/ethnicity: Results from the 2016 California Health Interview Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 37.
Abstract 3546: DFMO based improvement in survival of pancreatic cancer-bearing mice is associated with modulation of immune suppression in the tumor microenvironment
Authors: Sai Preethi Nakkina, Sarah B. Gitto, Jordan M. Beardsley, Veethika Pandey, Michael M. Rohr, Jignesh Parikh, Otto Phanstiel, Deborah A. Altomare
Journal: Cancer Research (2022)

Abstract Existing therapeutics have failed to improve pancreatic ductal adenocarcinoma (PDAC) patient outcomes, in part due to tumor associated immune suppression and upregulation of compensatory mechanisms. KRAS and c-MYC are important oncogenes in PDAC linked to tumor immune suppression. We describe the use of difluoromethylornithine (DFMO) and a c-RAF inhibitor (GW5074) to indirectly target c-MYC and KRAS, respectively. DFMO in combination with GW5074 was tested for ability to improve pancreatic cancer outcomes. Pancreatic cancer cells showed decreased cell viability and increased apoptosis in response to a combination of DFMO + GW5074. In vivo orthotopic models of pancreatic tumors had decreased tumor weight in DFMO + GW5074 treated mice, when compared to control group. However, only treatment with single agent DFMO resulted in improved survival of immunocompetent pancreatic tumor bearing mice with respect to control, in contrast to treatment with GW5074 alone or DFMO + GW5074. To understand why the in vivo data was contrary to in vitro results, immunohistochemical analysis of immune cells in the tumor microenvironment was used to reveal increased expression of markers associated with anti-tumor effects such as CD86, CD3, CD4 and CD8 in DFMO treated tumors. Tumors treated with DFMO also displayed decreased expression of MYC, suggesting that DFMO-associated MYC suppression could be linked to decreased immune suppression in the tumor microenvironment and improved survival. In contrast, GW5074 treatment maintained MYC expression in tumors. Overall, the present study points to DFMO being an immunomodulatory agent, and a need for further understanding of DFMO-based therapeutic strategies in PDAC. Citation Format: Sai Preethi Nakkina, Sarah B. Gitto, Jordan M. Beardsley, Veethika Pandey, Michael M. Rohr, Jignesh Parikh, Otto Phanstiel, Deborah A. Altomare. DFMO based improvement in survival of pancreatic cancer-bearing mice is associated with modulation of immune suppression in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3546.
Abstract 915: C/EBPβis required for mouse mammary tumorigenesis
Authors: Caitlin M. Burke, Michelle D. Rojo, Jeffery M. Rosen, Tobias Ackermann, Christine Muller, Cornelis F. Calkhoven, Heather L. Machado
Journal: Cancer Research (2022)

Abstract Breast tumorigenesis relies on complex interactions between tumor cells and their surrounding environment, orchestrated by tightly regulated transcriptional networks. While much is known about the signaling pathways affecting breast cancer cell growth and apoptosis, the transcriptional programs driving these responses are less understood. C/EBPβ is a transcription factor essential for proper cellular proliferation, differentiation, tissue function, metabolism, and the immune response, and is deregulated in breast cancer. C/EBPβ and its protein isoform LIP have long been postulated to promote breast cancer progression, however, the precise mechanisms and gene regulatory networks induced by C/EBPβ are less understood. Analysis of available human patient gene expression data reveals that increased Cebpb mRNA is associated with poor overall survival amongst all breast cancer subtypes, and analysis of available liquid chromatography with tandem mass spectrometry data shows that increased C/EBPβ total protein is associated with poor overall survival in triple-negative breast cancer patients. To test the function of C/EBPβ in tumor initiation and progression, several genetic mouse models were generated. Genetic ablation of tumor C/EBPβ in mouse models of basal-like [C3(1)TAg] and luminal (MMTV-Neu) breast cancers results in a complete block in mammary tumorigenesis. Interestingly, C/EBPβ-null tumor cells upregulate genes involved in antigen presentation and interferon gamma response in vitro, while overexpression of the C/EBPβ-LIP induces chemokines involved in immune cell recruitment and immunosuppression, such as CCL5. In support, RNA sequencing of human breast cancer cells shows that deletion of Cebpb in BT-20 cells causes de-repression of immune genes. Specifically, genes associated with interferon α and γ signaling (JAK1, TNFA, CCRL16, CSF2, IL32) as well as genes involved in antigen processing and presentation (MHC class I and class II molecules) are upregulated in the absence of Cebpb. These data suggest that C/EBPβ may repress genes important for immune visibility. Ongoing studies are aimed at identifying gene regulatory programs induced by C/EBPβ and specifically by C/EBPβ-LIP. These studies will have critical implications for whether C/EBPβ-induced pathways can be targeted in combination with other drugs, such as immune checkpoint inhibitors, improving patient outcome. These studies are supported by NIH RO1CA212518 (H.L.M.). Citation Format: Caitlin M. Burke, Michelle D. Rojo, Jeffery M. Rosen, Tobias Ackermann, Christine Muller, Cornelis F. Calkhoven, Heather L. Machado. C/EBPβis required for mouse mammary tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 915.
Abstract 3021: Understanding the effects of a ketogenic diet against pancreatic cancer
Authors: Omid Hajihassani, Ali Vaziri-Gohar, Mehrdad Zarei, Jonathan Hue, Helen Cheng, Anusha Mudigonda, Erryk Katayama, Hallie Graor, Jordan Winter
Journal: Cancer Research (2022)

Abstract With an overall survival of less than 3%, pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer-related death in the U.S. at its advanced stages. With the most promising therapeutics, the overall survival after a stage IV PDAC diagnosis is only at 11.1 months. The marginal effects of current therapeutics emphasize the importance of developing new approaches to treat PDAC. In a wide range of cancer subtypes, a ketogenic diet has shown encouraging effects as combination therapy. However, the underlying anti-tumorigenic pathways involved in this diet alone are still not well understood. The ketogenic diet’s core elements and direct physiologic effects (ketone bodies, fatty acids, low glucose, low insulin levels) potentially alter PDAC biology that span from redox homeostasis to mitochondrial metabolism, and epigenetic modifications. We hypothesized that in carefully controlled in vitro and in vivo experiments, KD components delay growth of PDAC. Additionally, we hypothesize that understanding the underlying drivers of the anti-tumor effects of a ketogenic diet could be leveraged into the rational design of combination therapies that augment these anti-tumor effects. We show that in the subcutaneous mouse model of PDAC, tumor growth is markedly delayed under ketogenic diet restrictions Furthermore, in PDAC cell culture models, we observed anti-cancer effects when the ketogenic diet core elements are isolated. Specifically, fatty acids and ketone bodies inhibit PDAC cell growth, particularly under high glucose conditions. These effects are somewhat attenuated under low glucose, suggesting that these elements result in competing effects on PDAC cells (i.e., support some pro-survival pathways while inhibiting others). Future studies seek to better delineate the mechanistic impact of the principal ketogenic diet elements on metabolic pathways with a focus on mitochondrial metabolism, as well effects on epigenetic signaling. Citation Format: Omid Hajihassani, Ali Vaziri-Gohar, Mehrdad Zarei, Jonathan Hue, Helen Cheng, Anusha Mudigonda, Erryk Katayama, Hallie Graor, Jordan Winter. Understanding the effects of a ketogenic diet against pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3021.
Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation
Authors: Derek W. Russell, Jonathan D. Casey, Kevin W. Gibbs, Shekhar Ghamande, James M. Dargin, Derek J. Vonderhaar, Aaron M. Joffe, Akram Khan, Matthew E. Prekker, Joseph M. Brewer, Simanta Dutta, Janna S. Landsperger, Heath D. White, Sarah W. Robison, Joanne M. Wozniak, Susan Stempek, Christopher R. Barnes, Olivia F. Krol, Alejandro C. Arroliga, Tasnim Lat, Sheetal Gandotra, Swati Gulati, Itay Bentov, Andrew M. Walters, Kevin M. Dischert, Stephanie Nonas, Brian E. Driver, Li Wang, Christopher J. Lindsell, Wesley H. Self, Todd W. Rice, David R. Janz, Matthew W. Semler, Stephen P. Peters, Muhammad Ali, Rita N. Bakhru, Scott Bauer, Christina R. Bellinger, Amanda M. Brown, Blair Brown, Jerri Brown, Caitlin Bumgarner, Wendy Butcher, Megan Caudle, Arjun B. Chatterjee, David J. Chodos, Gerardo Corcino, Nathan S. Cutler, Travis L. Dotson, Daniel C. Files, Jonathan L Forbes, John P. Gaillard, Katherine A. Gershner, Shannon Ginty, Kiadrick R. Hood, April Hazelwood, Katherine Hendricks, Kelly Jacobus, Jonathan T. Jaffe, Stacy Kay, Chad A. Kloefkorn, Jennifer Krall, Margo T. Lannan, Cornelia Lane, Cynthia Lanning, Jessica Lyons, William I. Mariencheck, Chad R. Marion, Matthew A. Maslonka, Sara McClintock, Nathaniel M. Meier, Matthew C. Miles, Peter J. Miller, Sophia Mitchell, Wendy C. Moore, Katherine Moss, Andrew M. Namen, Dustin L. Norton, Stella B. Ogake, Jill A. Ohar, Victor E. Ortega, Jessica A. Palakshappa, Rodolfo M. Pascual, Sandi Pascual, Aaron Pickens, Himanshu Rawal, Adam R Schertz, Matt Strong, Alexander O. Sy, Braghadheeswar Thyagarajan, Amy Townsend, Russell Worthen, Michael Wlodarski, Charles Yarbrough, Caroline York, Bradley Lloyd, Christopher Adler, Ahmed Agameya, Michael Colancecco, Daniel Fitelson, Joshua Giaccotto, Gena Han, Louise Kane, Ezra Miller, Timothy Noland, Jaqueline Price, Joseph Plourde, Emily Adams, Fraser Mackay, Laura Mahoney, Avignat Patel, Michael Plourde, Zena Saadeh, Sara Shadchehr, Sandeep Somalaraju, Eleanor Summerhill, Ryan Webster, Jordan Winnicki, Ekaterina Yavarovich, Anna Altz-Stamm, Cristina Bardita, Mary Clay Boone, Joe W. Chiles, Kristina Collins, Abby Drescher, Kevin G. Dsouza, Janna Dunn, Stacy Ejem, Josh Gautney, Nicole Harris, Savannah Herder, Tamer Hudali, R. Chad Wade, Rutwij Joshi, Daniel Kelmenson, Anne Merrill Mason, Scott R. Merriman, Takudzwa Mkorombindo, Megan Moore, Jada Nowak, Kate O’Connor, David B. Page, Sheylan D. Patel, G. Bruno Pereira, Lisa Sarratt, Tabitha Stewart, William S. Stigler, Kadambari Vijaykumar, Gina White, Micah R. Whitson, Katherine O. Heller, C. Cole Malibiran, Milad K. Jouzestani, Chandani Anandkat Zachary Zouyed, Matthew G. Drake, Makrina N. Kamel
Journal: JAMA (2022)

Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain.
Abstract 1625: c-Myc inhibition in prostate cancer cell lines
Authors: Carlos Riveros, Victor Chalfant, Sanjeev Shukla, Teruko Osumi, KC Balaji
Journal: Cancer Research (2022)

Abstract The proto-oncogene c-Myc is a transcription factor that is upregulated in several human cancers. Despite its key role, therapeutic targeting of c-Myc remains a challenge because of a disordered protein tertiary structure. The basic helical structure and zipper protein of c-Myc forms an obligate heterodimer with its partner MAX to function as a transcription factor. An attractive strategy is to inhibit MYC/MAX dimerization to decrease c-Myc transcriptional function. Several methods have been described to inhibit MYC/MAX dimerization including small molecular inhibitors and proteomimetics. We used NOD SCID gamma mice (NGS mice) that are immunodeficient, non-obese diabetic laboratory mice (Jackson Laboratories, Cat Number J000077451) carrying patient-derived xenograft (PDX) following implantation of grade IV adenocarcinoma of the prostate from a patient into the flanks of each mouse. For maximum tolerable dose studies, we used C57BL/6 wild type mice (Jackson Laboratories, Cat Number J000664). We performed a maximum dose tolerability study with the drug 3JC48-3 up to 100 mg/kg to determine limiting toxicity. We monitored the rate of growth for 2 weeks and measured the final volume of the tumors. Immunoprecipitation studies were performed using the prostate cancer cell line, PC-3, that were treated with the drug 3JC48-3 at different doses (0, 5, 10, and 20uM) for 24 hours and subsequently lysed. We found 3JC48-3 decreases prostate cancer growth and viability in a dose-dependent fashion in vitro. We confirmed the inhibition of MYC/MAX dimerization by 3JC48-3 using immunoprecipitation experiments. Normal mice and mice with patient-derived prostate cancer xenografts (PDX) tolerated intraperitoneal injections of 3JC48-3 up to 100 mg/kg body weight without dose-limiting toxicity. Preliminary results in these PDX mouse models suggest that 3JC48-3 may be effective in decreasing the rate of tumor growth. Our study demonstrates that 3JC48-3 is a potent MYC/MAX heterodimerization inhibitor that decreases prostate cancer growth and viability in association with upregulation of both PrKD1 expression and kinase activity. In addition, 3JC48-3 is well tolerated in prostate cancer PDX mice models and may be a candidate drug for further preclinical development. Citation Format: Carlos Riveros, Victor Chalfant, Sanjeev Shukla, Teruko Osumi, KC Balaji. c-Myc inhibition in prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1625.
Abstract 108: Insulin-like growth factor binding protein 4 exerts differential effects on breast cancer cell proliferation based on the expression status of pregnancy-associated plasma protein A
Authors: Keenan L. Flynn, Kevin D. Houston
Journal: Cancer Research (2022)

Abstract Insulin-Like Growth Factor Binding Protein 4 (IGFBP-4) is one of six binding proteins involved in sequestering insulin-like growth factors 1 and 2 (IGFs). IGFBP-4 expression is induced by estrogen receptor α (ERα), and its classical function is to prevent activation of IGF-1 receptor (IGF-1R) by sequestration of IGF-1. However, the aggressive triple-negative breast cancer cell line MDA-MB-231 shows high expression of IGFBP-4 along with its protease, pregnancy-associated plasma protein A (PAPP-A). Further, inhibition of IGFBP-4 in MDA-MB-231 cells is sufficient to reduce migration. To better understand the function of IGFBP-4 as a pro-cancer or anti-cancer protein, its anti-proliferative effects in ERα positive cells must be reconciled with its pro-migratory effects in triple negative cells. The role of IGFBP-4 in proliferation across four breast cancer cell lines representing ERα positive and triple negative subtypes was investigated. Stable transfection with IGFBP-4 expression construct in the MCF-7 and T-47D cell lines, which have silenced the PAPP-A gene, shows a reduction in proliferation. Further, MCF-7 parental cells cultured in conditioned media containing IGFBP-4 also show reduced proliferation, suggesting that the anti-proliferative effect of IGFBP-4 is associated with the absence of PAPP-A. Stable IGFBP-4 transfection of triple-negative MDA-MB-468 cell line, which has low extracellular IGFBP-4 when compared to MDA-MB-231 but does express PAPP-A, was sufficient to increase proliferation. Taken together, these results support the conclusion that proliferative effects of IGFBP-4 are dependent upon the expression status of PAPP-A. Citation Format: Keenan L. Flynn, Kevin D. Houston. Insulin-like growth factor binding protein 4 exerts differential effects on breast cancer cell proliferation based on the expression status of pregnancy-associated plasma protein A [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 108.
Abstract CT161: GP2 immune response a predictor of recurrence in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with breast cancer
Authors: Snehal S. Patel, David B. McWilliams, Mira S. Patel, Jaye Thompson, F. Joseph Daugherty
Journal: Cancer Research (2022)

Abstract The authors did not submit an updated abstract. The original abstract should be considered final. Citation Format: Snehal S. Patel, David B. McWilliams, Mira S. Patel, Jaye Thompson, F. Joseph Daugherty. GP2 immune response a predictor of recurrence in a phase IIb study evaluating HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT161.
Abstract 5572: T cell receptor modified with EDB-targeting ScFv and CD28 intracellular domain led to complete tumor regression in xenograft model
Authors: Zhijie Zhang, Wen Qiu, Chang Liu, Muhan Wang, Yinghua Miao, Qingchao Ji, Rongchen Sun, Hongping Yin, Meijia Yang
Journal: Cancer Research (2022)

Abstract We explored use of chimeric antigen receptor T cell (CAR-T) for treatment of solid tumors, aiming at efficient killing of tumor cells while minimizing on-target off-tumor toxicities. We designed CAR targeting the extra domain B (EDB)-containing fibronectin, which is an oncofetal antigen widely expressed in tumor stroma and on the surface of cancer cells. Unlike membrane-spanning antigens, EDB-containing fibronectin is embedded in the extracellular matrix, and is enriched in new vasculatures and stromal tissues of tumor tissues. First, we made a second-generation EDB CAR (2G-EDB CAR) that killed EDB+ cells (U87MG, A549, and HUVEC) and showed tumor suppression in a U87MG xenograft tumor model. However, while in vitro the 2G-EDB CAR T cells were sufficiently cytotoxic, the in vivo inhibition of the tumor growth was moderate. Next we designed an EDB CAR that contained CD3ε to create 3ε-EDB CAR. We show that the 3ε-EDB CAR was incorporated into the T cell receptor (TCR) structure. The 3ε-EDB CAR completely displaced the native CD3ε in the TCR based on immune precipitation and Western analysis. The 3ε-EDB CAR was capable of inducing T cell activation and proliferation in the presence of EDB-fibronectin antigen. Further, the 3ε-EDB CAR T cells killed tumor cells containing EDB-fibronectin. In vivo, the 3ε-EDB CAR T cells demonstrated improved inhibition when compared to the 2G-EDB CAR T cells. To further enhance the EDB-targeting CAR, we added intracellular domain of CD28 to the 3ε-EDB CAR to create 3ε28-EDB CAR, and showed the 3ε28-EDB CAR was still incorporated into the TCR complex. The 3ε28-EDB CAR co-opted TCR complex and provided co-stimulatory signal upon binding of EDB antigens. Upon transduction of the 3ε28-EDB CAR into primary T cells, we observed upregulation of T cell activation markers CD25, CD69 and granzyme B in presence of the EDB antigen. We show that 3ε28-EDB CAR triggered the phosphorylation of CD3ζ, suggesting that EDB antigen stimulated co-opted TCR and signaled through the TCR-CD3 complex. T cells transduced with 3ε28-EDB CAR demonstrated stronger proliferation when activated by U87MG cells compared to 2G or 3ε-EDB CARs. Furthermore, 3ε28-EDB CAR T cells inhibited in vivo tumor growth in a dose-dependent manner, and most of the treated mice had no evidence of residual tumors. In conclusion, our results suggest that 3ε28-EDB CAR has great potential for treatment of solid tumors. Citation Format: Zhijie Zhang, Wen Qiu, Chang Liu, Muhan Wang, Yinghua Miao, Qingchao Ji, Rongchen Sun, Hongping Yin, Meijia Yang. T cell receptor modified with EDB-targeting ScFv and CD28 intracellular domain led to complete tumor regression in xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5572.